scholarly journals Importance of Eosinophilic Infiltration of the Colonic Mucosa in Ulcerative Colitis Patients who are Refractory to Maintenance Therapy

2022 ◽  
Author(s):  
Takahiro Miyazu ◽  
Natsuki Ishida ◽  
Yusuke Asai ◽  
Satoshi Tamura ◽  
Shinya Tani ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Maintenance Therapy ◽  
Colonic Mucosa ◽  
Eosinophilic Infiltration ◽  
Pathological Examination ◽  
Clinical Activity ◽  
Short Term ◽  
Steroid Use ◽  
Steroid Administration ◽  
Before And After

Abstract Eosinophilic infiltration is sometimes observed histologically in ulcerative colitis (UC), but the effect of the degree of infiltration on the treatment course for UC is not completely studied. We investigated whether short-term steroid administration in UC patients refractory to maintenance therapy, with high eosinophilic infiltration in the colonic mucosa, contributed to clinical and endoscopic improvement. Ten patients with endoscopically active and pathologically high eosinophilic infiltration, based on pathological examination using endoscopic biopsy, were examined for clinical background when starting steroid treatment; clinical and endoscopic improvement before and after steroid use were assessed prospectively. The average initial steroid dosage and duration of use were 21.0 mg and 102.7 days, respectively. The mean values before and after steroid use of clinical activity index, Mayo endoscopic subscore, and UC endoscopic index of severity were 2.4 and 1.0, 1.8 and 0.7, and 3.9 and 1.1, respectively. All these scores improved significantly after steroid use (P=0.04, P<0.01, P<0.01, respectively). Steroids were discontinued in all patients; no patients required steroid re-administration. There may be cases of UC with eosinophilic infiltration into the colonic mucosa and resistant to maintenance treatment, suggesting that short-term steroid administration may contribute to clinical and endoscopic improvements.

scholarly journals P434 Effectiveness and safety of ustekinumab in ulcerative colitis: real-world evidence from Eneida Registry

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S394-S395
Author(s):  
M Chaparro ◽  
A Garre ◽  
M Iborra ◽  
M Barreiro-de Acosta ◽  
M J Casanova ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Real Life ◽  
Development Program ◽  
Analysis Data ◽  
Lower Probability ◽  
Clinical Activity ◽  
Short Term ◽  
Mayo Score ◽  
Patient Status ◽  
Probability Of Response

Abstract Background Ustekinumab has shown promising results in ulcerative colitis (UC) in the development program (UNIFI) that should be confirmed in clinical practice. Our aim was to evaluate the effectiveness and safety of ustekinumab in UC in real life. Methods Patients included in the prospectively maintained ENEIDA registry that received at least 1 dose of ustekinumab intravenously due to active UC were included. Clinical activity and effectiveness were defined based on Partial Mayo Score (PMS). The short-term response was assessed at week 8 and 16. The last-observation-carried-forward method was used in patients that stopped ustekinumab treatment before week 8 or 16. Variables associated with short-term remission were identified by logistic regression analysis. Data quality was assessed by remote monitoring. Results Forty-seven patients were included (Table 1); all of them had been previously exposed to biologic agents (70% to &gt;2): 100% to anti-TNF and 83% to vedolizumab. A total of 26% had been exposed to tofacitinib. Seventeen patients (36%) had response at week 8 [3 of them (6%) had remission]; 16 patients (34%) had response at week 16 [5 of them (11%) had remission] (Figure 1). There was a statistically significant decrease in C-reactive protein (CRP) concentration during the induction only in patients with a response at week 16 (Figure 2). The proportion of patients with CRP elevated at baseline and at week 8 was higher among non-responders at week 16 (Table 2). In the multivariate analysis, higher PMS at week 8 [odds ratio (OR) = 0.5; 95% confidence interval (CI) = 0.3–0.9)] and CRP over the upper normal limit at week 8 (OR = 0.1; 95% CI = 0.01–0.8) were associated with lower probability of response at week 16; steroids during induction increased the probability of response at week 16 (OR = 8; 95% CI = 1–71). Of patients without response at week 8, only 7% achieved response at week 16. Seventeen out of 31 patients continued ustekinumab beyond week 16, despite being non-responders. Of these 17 patients, 4 reached remission after the third dose, 1 after the fifth and 1 after the seventh one. There were 2 infections, one of them with fatal consequences (in a patient under steroids and tacrolimus due to renal transplant). Conclusion Ustekinumab shows benefit in some UC patients in real practice, even in a very refractory cohort in which the drug was prescribed as last resort. Patient status at week 8 seems to be a good predictor of response after the induction. Safety was consistent with the known profile of ustekinumab.

scholarly journals P710 The influence of probiotics to the efficacy of 5-ASA for the patients of ulcerative colitis

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S573-S574
Author(s):  
R YASUDA ◽  
K Uchiyama ◽  
T Takagi ◽  
M Kubota ◽  
S Sugino ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Colonic Mucosa ◽  
Activity Index ◽  
Time Dependent ◽  
Clinical Activity ◽  
Release Formulation ◽  
Significant Difference ◽  
Ph Dependent ◽  
Disease Location ◽  
Index Disease

Abstract Background 5-ASA is a key drug to treat the patients with mild-to-moderate ulcerative colitis (UC). Probiotics is sometimes used to UC patients for the purpose to correct dysbiosis of intestine. In theory, the efficacy of 5-ASA, especially pH-dependent release formulation of mesalazine may be weakened by the co-treatment with probiotics because of its effect leading to acidic condition in large intestine. However, the detail analysis about UC patients treating with 5-ASA and probiotics has not been elucidated. In the present study, we demonstrated the clinical course of UC patients treated by 5-ASA with probiotics to investigate the effect of probiotics to 5-ASA treatment. Methods The subjects were 85 UC patients who were in clinical remission and taking 5-ASA at the hospital of Kyoto Prefectural University of Medicine from January to March 2014. The clinical characteristics (age, sex, clinical activity index, disease location, and type of 5-ASA) and the rate of relapse until October 2019 were compared between probiotics group and no probiotics group. Furthermore, the rates of relapse were analysed for each specific 5-ASA between probiotics user and no probiotics user. The clinical activity index (CAI) was determined using Lichtiger index. The relapse of UC is defined by the increase of CAI, additional medication for UC, and endoscopic deterioration of colonic mucosa. Results Patients were included 39 cases in probiotics group and 46 cases in no probiotics group. There was no significant difference between probiotics and no probiotics group on the average age (53.1 ± 16.8 vs. 51.3 ± 14.2 years old, p = 0.59), the rate of male gender (41.0% vs. 41.3%, p =0.97), the average CAI (2.1 ± 0.64 vs. 2.0 ± 0.73, p = 0.59), disease location (extensive/left/rectum: 20/7/12 vs. 21/10/15 cases, p = 0.31), and type of 5-ASA (salazosulfapyridine/time-dependent mesalazine/pH-dependent mesalazine: 5/18/16 vs. 6/18/22 cases, p = 0.46). Besides, there was no significant difference between probiotics group and no probiotics group (51.3% vs. 52.2%, p = 0.93) about the rate of relapse. Regarding each specific 5-ASA usage, there was no significant difference on salazosulfapyridine (40.0% vs. 33.3%, p = 1), time-dependent mesalazine (44.4% vs. 50.0%, p = 1), and pH-dependent mesalazine (62.5% vs. 59.1%, p = 0.90) between probiotics user and no probiotics user. Conclusion In the present study, the co-treatment with probiotics did not affect the relapse with UC patients regardless the type of 5-ASA, suggesting that the usage of probiotics might not disturb the efficacy of 5-ASA for UC patients.

scholarly journals P489 Rescue treatment with original versus biosimilar infliximab in biologic-naïve patients with moderate-severe Ulcerative Colitis and corticosteroid failure

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S475-S475
Author(s):  
C Muñoz-Villafranca ◽  
M Á Ogueta ◽  
P Ramírez de la Piscina ◽  
B Álvarez-Herrero ◽  
A Loizate ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Colonic Mucosa ◽  
Rescue Therapy ◽  
Basque Country ◽  
Clinical Activity ◽  
Severe Ulcerative Colitis ◽  
Mayo Score ◽  
Rescue Treatment ◽  
Significant Difference ◽  
One Year

Abstract Background Infliximab is effective as rescue therapy in moderate-severe Ulcerative Colitis (UC). Subsequently, a biosimilar of infliximab has been approved for the same indications, as its effectiveness is considered similar to the original infliximab. Our aim was to analyse the colectomy rate and the efficacy of original infliximab (Remicade®) versus biosimilar infliximab (Inflectra®) in patients with moderate-severe UC who failed to respond to intravenous corticosteroids. Methods We performed a retrospective and observational study in two hospitals in the Basque Country. All patients hospitalised between 2010–2020 with moderate-severe UC, without response to intravenous corticosteroids and rescue treatment with infliximab were consecutively included. Two cohorts were established: the first one from 2010 to 2015 in patients treated with Remicade®, and the second one from 2015 to 2020 in patients with Inflectra®. We assessed all patients that had received at least one dose of infliximab. Patients were followed for a period of one year until loss of response or colectomy. Early colectomy is the surgery performed until week 12, and late colectomy between week 12 and one year. At the moment of hospitalisation all patients were clinically and endoscopically evaluated by Mayo Score. The clinical response was assessed in week 14 and 52. Results A total of 85 patients were evaluated, 53 (64.4%) in Remicade® group and 32 (37.6%) in Inflectra® group. 21.17% (18/85) of the patients had a colectomy in one year. 77.7% of the colectomies took place in the first 12 weeks (14/18, 7 patient in each group). Rates of early (13.8% vs 21.9%, p=0.297) and late colectomy (17% vs 28.1%, p=0.223) showed a numerical but non-statistically significant difference in favour of Remicade®. Transfusion (OR=4.20, IC 95% [1.38–12.77], p=0.011) and the presence of cytomegalovirus in the colonic mucosa (OR=4.07, IC 95% [1.31–12.63], p=0.015) were univariate predictors of colectomy. A statistically significant difference was found in clinical remission at week 14 (49.1% vs 25%, p=0.040) but not at week 52 (73.7% vs 50%, p=0.074) in patients with Remicade® versus Inflectra®. Neither clinical activity nor mucosa activity showed relationship with risk of colectomy. Conclusion 1. The rescue therapy with infliximab in patients with moderate-severe Ulcerative Colitis who failed to respond to intravenous corticosteroids could show a favourable trend for Remicade® against Inflectra®. However, further research is needed to confirm it. 2. The need of transfusion and the presence of cytomegalovirus in the colonic mucosa could be predictive factors of colectomy.

scholarly journals P678 Effect of accelerated infliximab induction on short-term outcomes of paediatric acute severe ulcerative colitis

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S553-S554
Author(s):  
M B Coronel-Arismendi ◽  
G Pujol Muncunill ◽  
B Minguez-Rodríguez ◽  
S Feo-Ortego ◽  
L N Guevara-Caviedes ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Adverse Events ◽  
Inflammatory Markers ◽  
Analytical Data ◽  
Disease Onset ◽  
Clinical Activity ◽  
Short Term ◽  
Severe Ulcerative Colitis ◽  
Induction Regimen

Abstract Background Due to a higher inflammatory burden and a rapid clearance of infliximab (IFX) in Acute Severe ulcerative colitis (ASUC), the accelerated IFX induction may be considered (IFX up to 10 mg/kg per dose, at week 0, 1 and 4–5) in those patients who need to start second-line treatment. The aim of our study is to describe the short-term outcomes of ASUC pediatric patients who have received an accelerated IFX induction regimen in our Unit. Methods In a retrospective study we collected data from patients with ASUC who received treatment with accelerated IFX induction. We analyzed demographic, clinical and analytical data as well as treatment adverse events from medical records. The short-term outcomes (at the end of the induction and at 3 months) were analyzed based in the Paediatric Ulcerative Activity Index (PUCAI)) and analytical parameters (haemoglobin, C reactive protein (CRP), erythrocyte sedimentation rate (ESR) and albumin. Results Six patients with ASUC who received accelerated IFX induction were included (5 male; median age at diagnosis 10.5 years (IQR: 2–15); mean time from diagnosis to ASUC flare: 1.8 years (IQR: 0–9 years)). At disease onset, 5/6 patients presented with pancolonic involvement (E4) with an average PUCAI of 55 points. At ASUC flare all of them presented pancolonic involvement with a PUCAI over 65 points, 50% of them had anaemia, 66.6% elevation of inflammatory markers (CRP and/or ESR) and 50% hypoalbuminemia. The patients received an accelerated IFX induction with IFX at 10 mg/kg at 0, 1 and 4 - 5 weeks without adverse events. After accelerated IFX induction regimen 5/6 patients showed clinical response and normalisation of laboratory tests (haemoglobin, inflammatory markers and albumin). One patient presented treatment failure needing surgery (colectomy rate 16.6%). At 3 months follow-up, no new patients needed colectomy. One patient had an infusional reaction and was changed to Vedolizumab treatment maintaining remission, the other 4 patients were maintained on IFX treatment (1 clinical remission, 3 mild clinical activity). The overall colectomy rate after accelerated IFX induction remained in 16,6%. Conclusion In our cohort of ASUC patients treated with an accelerated IFX induction regimen we observed an 83.3% free colectomy rate at short-term, being this regimen a valid therapeutic option to avoid surgery. Prospective and comparative studies are needed to determine the efficacy of this strategy in reducing the colectomy rate, both in the short-and long-term follow-up.

Tofacitinib in Ulcerative Colitis: Real-world Evidence From the ENEIDA Registry

2020 ◽  
Author(s):  
María Chaparro ◽  
Ana Garre ◽  
Francisco Mesonero ◽  
Cristina Rodríguez ◽  
Manuel Barreiro-de Acosta ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Real Life ◽  
Lower Probability ◽  
Clinical Activity ◽  
Short Term ◽  
Mayo Score ◽  
Real World Evidence ◽  
Real Practice ◽  
Term Response ◽  
Over Time

Abstract Aim To evaluate the effectiveness and safety of tofacitinib in ulcerative colitis [UC] in real life. Methods Patients from the prospectively maintained ENEIDA registry and treated with tofacitinib due to active UC were included. Clinical activity and effectiveness were defined based on Partial Mayo Score [PMS]. Short-term response/remission was assessed at Weeks 4, 8, and 16. Results A total of 113 patients were included. They were exposed to tofacitinib for a median time of 44 weeks. Response and remission at Week 8 were 60% and 31%, respectively. In multivariate analysis, higher PMS at Week 4 (odds ratio [OR] = 0].2; 95% confidence interval [CI] = 0].1–0.4) was the only variable associated with lower likelihood of achieving remission at Week 8. Higher PMS at Week 4 [OR = 0.5; 95% CI = 0.3–0.7] and higher PMS at Week 8 [OR = 0.2; 95% CI = 0.1–0.5] were associated with lower probability of achieving remission at Week 16. A total of 45 patients [40%] discontinued tofacitinib over time. Higher PMS at Week 8 was the only factor associated with higher tofacitinib discontinuation [hazard ratio = 1.5; 95% CI = 1.3–1.6]. A total of 34 patients had remission at Week 8; of these, 65% had relapsed 52 weeks after achieving remission; the dose was increased to 10 mg/12 h in nine patients, and five of them reached remission again. Seventeen patients had adverse events. Conclusions Tofacitinib is effective and safe in UC patients in real practice, even in a highly refractory cohort. A relevant proportion of patients discontinue the drug over time, mainly due to primary failure.

scholarly journals OP29 Tofacitinib in ulcerative colitis: Real-world evidence from Eneida Registry

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S026-S028 ◽  
Author(s):  
M Chaparro ◽  
A Garre ◽  
F Mesonero ◽  
C Rodríguez ◽  
M Barreiro-de Acosta ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Regression Analysis ◽  
Cox Regression ◽  
Retention Rate ◽  
Real Life ◽  
Lower Probability ◽  
Clinical Activity ◽  
Short Term ◽  
Cox Regression Analysis ◽  
Over Time

Abstract Background Our aim was to evaluate the effectiveness and safety of tofacitinib in ulcerative colitis (UC) in real life. Methods Patients from the prospectively maintained ENEIDA registry treated with tofacitinib due to active UC were included. Clinical activity and effectiveness were defined based on Partial Mayo Score (PMS). The short-term response was assessed at week 4, 8 and 16. The last-observation-carried-forward method was used in patients that stopped tofacitinib before the time-points for clinical assessment. Variables associated with short-term remission at week 8 were identified by logistic regression analysis. The cumulative retention rate and the cumulative incidence of relapse over time were assessed by survival curves. Cox-regression analysis was performed to identify predictive factors of tofacitinib discontinuation or relapse over time. Data quality was assessed by remote monitoring. Results 113 patients were included (Table 1 and Figure 1) and exposed to tofacitinib a median of 44 (interquartile range = 30–66) weeks. Response and remission at week 8 were 60% and 31%, respectively (Figure 2). In multivariate analysis, higher PMS at week 4 [odds ratio (OR)=0.2; 95% confidence interval (CI) = 0.1–0.4] was the only variable associated with the likeliness of achieving remission at week 8. Higher PMS at week 4 (OR = 0.5; 95% CI = 0.3–0.7) and higher PMS at week 8 (OR = 0.2; 95% CI = 0.1–0.5) were associated with lower probability of achieving remission at week 16. Twenty per cent of those without remission at week 4, and 12% of those without remission at week 8, achieved remission at week 16. A total of 45 patients (40%) discontinued tofacitinib over time (Figure 3); the discontinuation rate was 34% and 46% at 24 and 52 weeks, respectively. PMS at week 8 was the only factor associated with tofacitinib discontinuation [Hazard ratio (HR) = 1.5; 95% CI = 1.3–1.6)]. A total of 33 patients had remission at week 8; from them, 65% relapsed 52 weeks after achieving remission; 9 patients increased the dose to 10 mg /12 h and 5 reached remission again. No factors associated with relapse over time were identified. Eighteen patients had adverse events (4 hypercholesterolaemia, 2 herpes zoster, 3 infections, 2 dyspnoea, 1 neoplasia, 1 lymphopenia, 1 headache, 1 hypertriglyceridaemia and 4 others). No thromboembolic events were reported. Conclusion Tofacitinib is relatively effective in UC patients in real practice even in a highly refractory cohort. Only 10% of the patients without remission at week 8 reached remission at week 16. A relevant proportion of patients discontinue the drug over time, mainly due to primary failure. Over 60% of patients that achieve remission, relapse over time. Safety was consistent with the known profile of tofacitinib

Upregulation of GRAIL is associated with remission of ulcerative colitis

2008 ◽  
Vol 295 (1) ◽  
pp. G163-G169 ◽  
Author(s):  
Satoshi Egawa ◽  
Hideki Iijima ◽  
Shinichiro Shinzaki ◽  
Sachiko Nakajima ◽  
Jun Wang ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
T Cells ◽  
Mrna Expression ◽  
Activity Index ◽  
Clinical Activity ◽  
E3 Ligases ◽  
T Cell Anergy ◽  
Before And After ◽  
Anergic T Cells ◽  
Active Disease

Abrogating tolerance against unidentified antigens is a critical step in the pathogenesis of ulcerative colitis (UC). T cell anergy, one of the main mechanisms of tolerance, has been shown to be induced by E3 ubiquitin ligases, such as gene related to anergy in lymphocytes (GRAIL), Itch, and c-Cbl in mice. However, it is not well known whether these E3 ligases play roles in human diseases. The pathophysiological role of the E3 ligases in patients with UC was investigated. At first, the expression of GRAIL, Itch, and c-Cbl in human anergic T cells was analyzed by quantitative RT-PCR and Western immunoblotting. Next, the mRNA expression of the E3 ligases was analyzed in peripheral CD4+ T cells of 20 patients with UC and 10 healthy volunteers (HV). mRNA expression was analyzed in patients with active UC before and after treatment with prednisolone and leukocytapheresis. Anergic human CD4+ T cells expressed significantly higher levels of GRAIL, Itch, and c-Cbl than nonanergic cells. GRAIL expression was significantly higher in patients with UC in remission than in patients with active disease and in HV ( P < 0.01). The level of GRAIL expression was also significantly increased in patients with active disease whose clinical activity index scores improved after treatment ( P < 0.05). There were no significant differences in Itch and c-Cbl expression among patients with active UC, patients with UC in remission, and HV. These data suggest that GRAIL plays an important role in maintaining remission in patients with UC.

P168 BACTEROIDETES SPECIES ARE USEFUL BIOMARKER OF CLINICAL ACTIVITY IN ULCERATIVE COLITIS

2020 ◽  
Vol 158 (3) ◽  
pp. S64-S65
Author(s):  
Kei Nomura ◽  
Dai Ishikawa ◽  
Koki Okahara ◽  
Shoko Ito ◽  
Masahito Takahashi ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Activity

TO STUDY THE EFFECT OF BMV ON P WAVE DISPERSION AND SHORT TERM PROGNOSTIC IMPACT OF P WAVE DISPERSION IN PREDICTION OF CLINICAL OUTCOME AFTER PERCUTANEOUS BALLOON MITRAL VALVULOPLASTY IN PATIENTS WITH MITRAL STENOSIS AND SINUS RHYTHM

2020 ◽  
Vol 4 (9) ◽  
Author(s):  
Ashish Kumar Agarwal ◽  
Daulat Singh Meena ◽  
Vijay Pathak ◽  
Anoop Jain ◽  
Rakesh Kumar Ola
Keyword(s):  
Clinical Outcome ◽  
Right Ventricular ◽  
Wave Dispersion ◽  
Tissue Doppler ◽  
P Wave ◽  
Short Term ◽  
P Wave Dispersion ◽  
Mitral Valvuloplasty ◽  
Percutaneous Balloon ◽  
Before And After

Background: The aim of the present study was to study the effect of percutaneous balloon mitral  valvuloplasty (PBMV) on P wave dispersion and to test the correlation between P-maximum and  P-dispersion to right ventricular function and pulmonary artery pressure before and after PMBV. Also to study the impact of P-maximum and P-wave dispersion on the short term clinical outcome after successful PBMV in patients with mitral stenosis (MS) and sinus rhythm. Methods: 75 patients undergoing PMBV were enrolled in this study. We evaluated P-maximum, P-minimum and P-wave dispersion before and one month and one year after PBMV . We studied the changes in pulmonary arterial pressure (PAP), left atrial (LA) dimension, mitral diastolic gradient, and mitral valve area, in addition to the changes in right ventricular function utilizing tissue Doppler assessment both before and after PMBV, in addition the role of the P-wave dispersion in prediction of late cardiac events. Results: There were significant decrease in mean diastolic gradient, PAP, and LA size and significant improvement in right ventricular tissue Doppler indices after PMBV. Accompany these hemodynamic changes after PMBV. P-maximum and P-wave dispersion were found to be decreased (P < 0.001). Conclusion: Successful PBMV was associated with a decrease in Pmax and PWD. These simple electrocardiographic indices may predict the success of the procedure immediately after PBMV.  The P-maximum and P-wave dispersion changes were correlated with significant impairment of right dysfunction and the degree of pulmonary artery pressure. Keywords: PBMV.PAP,LA

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